DBX Demineralized Bone Matrix. Thenatural solution for bone grafting needs.Safe donorsCareful processingQuality allograftsDBX demineralized bone matrix Cortical bone Demineralized bone powder Sodium hyaluronate carrierSynthes DBX Demineralized Bone MatrixDBXDemineralized Bone Matrix. The natural solution for bone grafting needs.DBX is demineralized bone matrix thathas osteoinductive potential* and is osteoconductive. It is composed ofdemineralized bone from humandonors in a biocompatible carrier. The various tissue forms have been designed to meet surgical needs whilemaximizing the amount of bone deliv-ered to the surgical site. The demineralized bone powder is produced by the removal of mineralsfrom cortical bone. DBX demineralizedbone matrix is nonhemolytic, ensuringcompatibility with the surrounding auto-genous blood cells. The DBX formulationhas been specifically designed to modelthe pH of human blood.Removeminerals+*Note: It is unknown how the osteoinductive potential, measured in the athymicmouse model or the alkaline phosphatase assay, will correlate with clinicalperformance in human subjects.Synthes 1Indications and ContraindicationsIndicationsDBX is intended for use as a deminer-alized bone matrix for voids or gapsthat are not intrinsic to the stability ofthe bony structure. DBX is indicated fortreatment of surgically created osseousdefects or osseous defects created fromtraumatic injury.Additionally, DBX Putty and Paste are intended for the augmentation ofdeficient maxillary and mandibularalveolar ridges and the treatment oforal/maxillofacial and dental intra-osseous defects. DBX is for single-patient use only.Contraindications*DBX is not intended to provide structuralsupport of the bone during the healingprocess. DBX is also contraindicated inthe following circumstances: Incomplete skull growth Severe vascular or neurological disease Fever Uncontrolled diabetes Severe degenerative bone disease Pregnancy Hypercalcemia Renal-compromised patients History of, or active Potts disease Osteomyelitis at the surgical site Sepsis in or around the surgical site Inability to cooperate with and/orcomprehend postoperative instructionsIndications for UseDBX DBX DBX DBX DBXPutty Inject Paste Mix StripExtremities Spine Posterolateral spine Pelvis Ridge augmentation Filling of extraction sites Cranium Craniofacial augmentation Mandibular reconstruction Repair of traumatic defects of the alveolar ridge, excluding maxillary and mandibular fractureFilling resection defects in benign tumors, benign cysts, or other osseous defects in the alveolar ridge wallFilling of cystic defect Filling of lesions of periodontal origin Filling of defects of endodontic origin DBX putty can be used as an extender in the spine with autograft. DBX can be used with bone marrow aspirate.*Please see Directions for Use for complete description of indications,contraindications, warnings and precautions.2 Synthes DBXDemineralized Bone MatrixDBX Putty Provides a moldable consistency Can be mixed with blood or bone marrow Composed of granulated cortical bone in sodium hyaluronate 31% bone content (by weight)DBX Inject DBX Putty with a delivery system Provides a moldable consistency direct from the deliverysystem Composed of granulated cortical bone in sodium hyaluronate Cannula and tamp available for more precise delivery (sold separately) 31% bone content (by weight)DBX Paste Provides a flowable consistency Composed of granulated cortical bone in sodium hyaluronate 26% bone content (by weight)DBX Mix Provides a morselized cortical-cancellous bone texture in sodium hyaluronate Eliminates or reduces the need to combine bone chipswith DBM 35% bone content (by weight)DBX Strip Provides a cohesive and flexible consistency in a preformedstrip formulation Combined with sodium hyaluronate and gelatin 45% bone content (by weight)All DBX formulations are designed to resist movement underirrigation while maintaining the physical integrity of the tissueform. Every lot of DBX undergoes strict release criteria testing.Sterility is tested per USP . Each lot is also tested via anin vitro or in vivo assay for osteoinductive potential. Excellent Handling PropertiesSynthes 3Carrier characteristicsSodium hyaluronate is a polysaccharide which occurs naturallyin the human body. It plays an essential role in cell proliferation,migration and adhesion, and has been correlated to angio-genesis.1,2It also confers positional stability to the tissue.3Sodium hyaluronate is proven to be safe.2The DBX Putty carrier, sodium hyaluronate, is similar to the naturally occurring hyaluronate found in the body. MTF uses high-quality medical grade sodium hyaluronate, producedthrough fermentation processes under good manufacturingpractice (GMP) guidelines.The DBX Putty formulation has been specifically designed to have the physiological normal pH of 7.2, similar to human blood.4 Synthes DBXDemineralized Bone MatrixOsteoinductive PotentialEach lot of DBX is validated in vivo or in vitro to verify its osteoinductive potential.MTF utilizes the following methods to measure DBM osteoinductive potential prior to distribution: Athymic mouse muscle pouch assay Alkaline phosphatase assayAthymic Mouse TestThe athymic mouse assay for in vivo osteoinductive potentialis based upon the Urist4model and is designed to histologi-cally confirm that DBX tissues have osteoinductive potentialprior to distribution. In this model, implantation of demineralized bone in thehamstring muscle pouch of an athymic mouse will result inectopic bone formation if the bone has osteoinductive potential. Alkaline Phosphatase (ALP) Test ALP is an enzyme produced by bone growing cells duringnew bone formation. Demineralized bone will activate thesebone growing cells, thus resulting in increased levels of theALP enzyme. Correlations between the ALP levels and in vivoosteoinductivity scores from the athymic mouse modeldemonstrate that the ALP assay can be used as anothermeans of measuring the osteoinductive potential of DBM tissue forms.5Each lot of DBX is validated using one or both of thesemethods. Synthes 5Important Factors of a Good DBMQuality tissue MTF potential donors must pass through an extensive quality assurance process and comprehensive medical andsocial history check A team of medical/technical specialists evaluates all infor-mation, including test results, before the donor is releasedfor processing MTF voluntarily exceeds both AATB and FDA screening criteria6Careful processing To maintain biological integrity, MTF processes all tissueusing aseptic techniques in ISO Class 4 (certified) cleanrooms MTF tissue is not terminally sterilizedA good carrier Sodium hyaluronate is a polysaccharide formed by plasmamembrane proteins in the human body Sodium hyaluronate naturally occurs in the human body in the joints, eyes, extracellular matrix of skin and muscu-loskeletal tissue Sodium hyaluronate plays an essential role in cell prolifera-tion, migration and adhesion and has been correlated toangiogenesis1, 2 Sodium hyaluronate used in DBX is high-quality, medicalgrade sodium hyaluronate, ISO 13485 certified, producedthrough fermentation processes using Good ManufacturingPractice (GMP) guidelinesQuality control Every lot of DBX undergoes strict release criteria testing Each lot is also tested via an in vitro or in vivo assay for osteoinductive potentialScientific evidence Numerous studies have demonstrated the clinical effective-ness of MTFs demineralized bone matrix forms7, 86 Synthes DBX Demineralized Bone MatrixClinical StudiesStudy 1: DBX Putty plus autograft has been shown tobe as effective as autograft aloneA mix of DBX Putty and autograft was shown to be as effective as autograft alone in a multicenter, randomized,controlled clinical study of patients undergoing posterolateralspine fusion for the treatment for degenerative disc disease(DDD).7 Equivalent fusion rates were achieved: DBX and autograft = 100% at 24 months Autograft alone = 96% at 24 months Both groups exhibited significant decrease in VAS painscores at 6 months relative to baseline that is sustainedthrough 24 months The authors conclude that DBX Putty is at least as effectiveas autograft alone when used as a bone graft extender inthe treatment of DDD via posterolateral spine fusion An equivalent fusion rate was achieved between the twogroups at 24 monthsStudy 2: DBX Putty effectively treats periodontalintraosseous defectsIntraosseous periodontal defects in systemically healthy patients were treated with either DBX putty or with deminer-alized freeze-dried bone allograft (DFDBA). Only sites withdefects 3 mm in depth were considered. A statistical analysis was conducted at 6 months postoperative. Bothgroups of patients yielded significant improvements in percent bone fill, with 37% 18.5% bone fill achieved inpatients treated with DFDBA and 50% 25% in case of patients treated with DBX.8Average Visual Analog Scale (VAS) pain scores over time for autograftalone (Autograft) and DBX with autograft (DBX) treatment groups.DBX group, 59-year-old womanat discharge showing an imma-ture, disorganized bone graftSame patient at 12 months,showing a fully matured fusion-mass with mineralizedbone graftSynthes 7Musculoskeletal Transplant Foundation (MTF) Synthes has partnered exclusively with the MusculoskeletalTransplant Foundation (MTF) for over 10 years to providehigh quality tissue for patients. Although there are nationalstandards for tissue banks, they only set a baseline for the industry. Beyond that, regulations leave a lot to interpretation, so standards vary significantly from tissuebank to tissue bank. MTF offers safe allografts processedfrom among the most carefully selected donors. Directed by SurgeonsMTF utilizes a Medical Board of Trustees comprised of more than forty surgeons from world-renowned academic institutions. MTFs board sets standards, which are amongsome of the most stringent in the industry. Selecting the Ideal DonorMTFs extensive network of participating organ procurementorganizations ensures that MTF has access to a broad selection of qualified donors. MTF holds itself to stringentstandards for donor selection and processing criteria. MTFdefers more donors than they accept. Preserving and Protecting Tissue IntegrityMTFs approach ensures a high level of safety, without compromising biological and mechanical integrity. Not allforms of human tissue are the same, nor should they beprocessed the same way. MTF has developed and validatedseveral tissue cleaning technologies to provide safe and high quality allograft bone. Since MTFs inception, MTF has maintained an exemplary safety record distributing almost 4.2 million allografts from nearly 80,000 donors.MTF Donor Deferral Rate> 97% deferred< 3% acceptedMTFs standards are set bytheir Medical Board of Trustees more than 40 surgeons fromworld-renowned academic institutions.8 Synthes DBX Demineralized Bone MatrixProduct InformationDBX Demineralized Bone MatrixPasteVolume (cc)028005 0.5028010 1.0028050 5.0028100 10.0DBX Demineralized Bone MatrixPuttyVolume (cc)038005 0.5038010 1.0038025 2.5038050 5.0038100 10.0DBX Demineralized Bone MatrixStripSize (cm)048010 2.5 x 10 (Spine)048125 2.5 x 5 (Trauma)048150 5 x 5 (Trauma)DBX Demineralized Bone MatrixMixVolume (cc)058025 2.5058050 5.0058100 10.0058200 20.0DBX Demineralized Bone MatrixInject(Spine and Trauma only)Volume (cc)068025 2.5068050 5.0068100 10.0Synthes 9References1. Fraser, J.R. and T.C. Laurent, Turnover and metabolism ofhyaluronan. Ciba Found Symp, 1989. 143: p. 4153; discussion 539, 2815.2. Orlidge A., P.A. DAmore, Cell specific effects of glycosaminoglycans on the attachment and proliferationof vascular wall components. Microvasc Res, 1986. 31(1): p. 4153.3. Gertzman, A. and M. Sunwoo. A pilot study evaluatingsodium hyaluronate as a carrier for freeze-dried demineral-ized bone powder. Cell and Tissue Banking, 2001(2): p. 8794.4. Urist M.R., Bone: Formation by autoinduction. Science,1965. 150(698): p. 8939.5. Han, B., B. Tang, and M.E. Nimni. Quantitative and sensitive in vitro assay for osteoinductive activity of demineralized bone matrix. J Orthop Res, 2003. 21(4): p. 64854.6. Jurgensmeier, D., R.A. Hart, J. Jones. 2008 Annual Meetingof the American Academy of Orthopaedic Surgeons (Book of Proceedings, abstract).7. Becker, V., et al., Comparison of autograft to DBX demineralized bone matrix putty combined with autograftused in posterolateral lumbar fusion. AANS 73rd AnnualMtg (2005), 2005.8. Bender, S.A., et al., Evaluation of demineralized bone matrix paste and putty in periodontal intraosseous defects. J Periodontal, 2005. 76(5): p. 76877. 2005 Synthes, Inc. or its affiliates. Synthes is a trademark of Synthes, Inc. or its affiliates.Printed in U.S.A.3/11J3261-FDBX is a registered trademark, and DBX Inject is a trademark of the Musculoskeletal Transplant Foundation. Available throughSynthes 1302 Wrights Lane EastWest Chester, PA19380Telephone: (610) 719-5000To order call: (800) 522-9069Fax: (877) 534-1560www.synthes.comProcessed byMusculoskeletal TransplantFoundation125 May StreetEdison, NJ08837Telephone: (732) 661-0202Fax: (732) 661-2298